Department of Anesthesiology, Third Xiangya Hospital of Central South University, Changsha, China.
J Clin Pharmacol. 2012 Jun;52(6):940-6. doi: 10.1177/0091270011406278. Epub 2011 Jun 16.
The aims of this study were to investigate the effect of quercetin on CYP3A activity in vivo. An open, randomized, 2-period crossover experiment was performed in 18 healthy male volunteers. Genotyped data were available from a total of 165 participants. The allelic frequency was 52.5%. Every volunteer ingested orally 500 mg quercetin or placebo once a day for 13 consecutive days. On day 14, a single 7.5-mg midazolam tablet was administrated orally. The plasma concentrations of midazolam and 1-OH-midazolam were determined over 24 hours. The results showed that coadministration of quercetin in CYP3A5*1/1 and CYP3A51/3 individuals significantly decreased the area under the curve (AUC(0-12 h)) of midazolam (160.88 ± 45.58 ng·h/mL vs 188.07 ± 65.75 ng·h/mL, P < .05), significantly decreased the AUC(0-∞) of midazolam (165.46 ± 47.15 ng·h/mL vs 211.84 ± 75.80 ng·h/mL, P < .01), shortened t(1/2) (2.06 ± 0.51 h vs 2.75 ± 0.89 h, P < .01), and decreased t(max) significantly (0.48 ± 0.36 h vs 1.06 ± 0.69 h, P < .01), respectively. In conclusion, quercetin significantly induced CYP3A activity to substrate midazolam, and the induction was partly related to the CYP3A5 genotype, being more prominent in CYP3A51/1 and CYP3A51/*3 individuals.
本研究旨在探讨槲皮素对体内 CYP3A 活性的影响。在 18 名健康男性志愿者中进行了一项开放、随机、2 期交叉试验。共有 165 名参与者提供了基因分型数据。等位基因频率为 52.5%。每位志愿者连续 13 天每天口服 500mg 槲皮素或安慰剂一次。第 14 天，口服单剂量 7.5mg 咪达唑仑片。测定 24 小时内咪达唑仑和 1-OH-咪达唑仑的血浆浓度。结果表明，CYP3A5*1/1 和 CYP3A51/3 个体同时服用槲皮素可显著降低咪达唑仑的 AUC(0-12 h)(160.88 ± 45.58ng·h/mL 比 188.07 ± 65.75ng·h/mL，P<.05)，显著降低咪达唑仑的 AUC(0-∞)(165.46 ± 47.15ng·h/mL 比 211.84 ± 75.80ng·h/mL，P<.01)，缩短 t1/2(2.06 ± 0.51h 比 2.75 ± 0.89h，P<.01)，并显著降低 tmax(0.48 ± 0.36h 比 1.06 ± 0.69h，P<.01)。总之，槲皮素显著诱导了咪达唑仑的 CYP3A 活性，这种诱导与 CYP3A5 基因型部分相关，在 CYP3A51/1 和 CYP3A51/*3 个体中更为显著。
